Diabetes mellitus is a disease of major global importance, increasing in frequency at almost epidemic rates, such that the worldwide prevalence in 2006 is 170 million people and predicted to at least double over the next 10-15 years. Diabetes is characterized by a chronically raised blood glucose concentration (hyperglycemia), due to a relative or absolute lack of the pancreatic hormone, insulin. Within the healthy pancreas, beta cells, located in the islets of Langerhans, continuously produce and secrete insulin in correspondence with blood glucose levels, maintaining near constant glucose levels in the body.
Much of the burden of the disease to the patients and to health care resources is due to long-term tissue complications, which affect both small blood vessels (microangiopathy, causing eye, kidney and nerve damage) and large blood vessels (causing accelerated atherosclerosis, with increased rates of coronary heart disease, peripheral vascular disease and stroke). The Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of the chronic complications of diabetes are greatly related to the degree of altered glycemia as quantified by determinations of glycohemoglobin (HbA1c) [DCCT Trial, N Engl J Med 1993; 329: 977-986, UKPDS Trial, Lancet 1998; 352: 837-853. BMJ 1998; 317, (7160): 703-13 and the EDIC Trial, N Engl J Med 2005; 353, (25): 2643-53]. Thus, maintaining euglycemia by frequent glucose measurements and adjustment of insulin delivery accordingly is of utmost importance.
Conventional insulin pumps can deliver rapid acting insulin 24 hours a day through a catheter placed under the skin. The total daily insulin dose can be divided into basal and bolus doses.
Insulin boluses are delivered before or after meals to counteract carbohydrates loads or during episodes of high blood sugar levels.
Basal insulin is delivered continuously over 24 hours, and keeps the blood glucose levels within acceptable ranges between meals and overnight. Diurnal basal rates can be pre-programmed or manually changed according to various daily activities.
Conventional insulin pumps provide an option to change basal delivery profile for a predetermined time period, as described in U.S. Patent Application No. 2007/006956 assigned to MiniMed. The user can change basal rate to a new rate (referred-to as “Temporary Basal Rate” or “TBR”) which can be a fixed percentage of the Current Basal Rate (hereinafter “CBR”) (i.e., the basal rate remains a percentage of a constant value). For example, if a CBR of 1 U/h at 12 am was followed by a reduction of 50% of the CBR for a period of time of 2 hours, a TBR of 0.5 U/h would result between 12 am and 2 am. After 2 am, the basal rate would typically return to the former CBR before the change, i.e. 1 U/h. It is worth noting, that the term “current” (as used with Current Basal Rate) is meant to mean the present/now (occurring presently) and/or anticipated, planned, prospective and programmed corresponding to future events.
In another example, the TBR may change its absolute value but maintain a fixed percentage of the prospective basal rate, i.e. the basal rate that would have otherwise been delivered. That is, the basal rate remains at a uniform percentage of the basal profile as it varies. For example, if the CBR was supposed to be 1 U/h between 8 am and 12 pm, and 2 U/h between 12 pm and 8 pm, a reduction of 50% of the CBR for a period of 4 hours starting at 10 am, would result in a TBR of 0.5 U/h between 10 am and 12 pm, and 1 U/h between 12 pm and 2 pm. After 2 pm, the basal rate would return to its prospective value, i.e. 2 U/h.
Such temporary changes in basal delivery rates appear to provide a convenient way to adjust insulin delivery in response to a temporary change in a user's daily activity.
Pharmacodynamic observations have shown that the time between basal delivery rate change and metabolic effect is very long (in the order of hours). The conventional basal rate changing methods as described above do not comply with human physiology because they do not consider this delay between basal delivery rate change and metabolic effect. For example, before extreme exercise a patient had reduced basal rate from 1 U/h to 0.5 U/h for 2 hours. In practice, steady state at 0.5 U/h was achieved after 2 hours. Consequently, the patient was overdosed during exercise and under dosed during recovery from exercise. This way, the application of temporary basal insulin delivery is being employed inefficiently and may risk patient's health.